The present invention relates to compositions of matter for reducing or maintaining intraocular pressure, and, more particularly, to a method and composition for reducing or maintaining intraocular pressure involving the administration of a 1,11-lactone of a prostaglandin or prostaglandin analog in an opthalmically acceptable medium.
The compositions and method of the present invention are particularly useful for the management of glaucoma, a disease of the eye characterized by increased intraocular pressure. On the basis of its etiology, glaucoma has been classified as primary or secondary. For example, primary glucoma in adults, e.g., congenital glaucoma, may be either chronic open-angle, or acute or chronic angle-closure. Secondary glaucoma results from preexisting ocular diseases such as uveitis, intraocular tumor or an enlarged cataract.
The underlying causes of primary glaucoma are not yet well known. The increased intraocular tension is typically due to obstruction of aqueous humor outflow. In chronic open-angle glaucoma, the anterior chamber and its anatomic structures appear normal but drainage of the aqueous humor is impeded. In acute and chronic angle-closure glaucoma, the anterior chambe is shallow, the filtration angle is narrowed and the iris may obstruct the trabecular meshwork at the entrance of the canal of Schlemn. Dilation of the pupil may push the root of the iris forward against the angle or may produce pupillary block and thus precipitate an acute attack. Eyes with narrow anterior chamber angles are predisposed to acute angle-closure glaucoma attacks of varying degrees of severity.
Secondary glaucoma is caused by any interference with the flow of aqueous humor from the posterior chamber into the anterior chamber and subsequently into the canal of Schlemm. Inflammatory disease of the anterior segment may prevent aqueous escape by causing complete posterior synechia in iris bombe, and may plug the drainage channel with exudates. Other common causes are intraocular tumors, enlarged cataracts, central retinal vein occlusion, trauma to the eye, operative procedures and intraocular hemorrhage.
Considering all types together, glaucoma occurs in about 2% of all persons over the age of 40, and may be asymptomatic for years before progressing to rapid loss of vision. In cases where surgery is not indicated, topical beta-adrenoceptor antagonists have traditionally been the drugs of choice for treatment.
Certain eicosanoids, particularly various prostaglandins, have been reported to possess ocular hypotensive activity. However, prostaglandin ocular hypotensives generally suffer from the disadvantage of inducing conjunctival hyperemia of varying severity and duration, smarting, and foreign body sensation as well as presenting solubility problems in certain ophthalmically advantageous carriers.
This invention relates to derivatives of the known prostaglandins formulated in a pharmaceutically acceptable vehicle, and ophthalmic used of these prostaglandins. The present invention has numerous advantages over the prior art, including increased duration of action and elimination or reduction of the aforementioned undesirable side effects, and easy solubilization in certain ophthalmically advantageous carriers.